注射用小干扰核糖核酸脂质体药效学研究

Pharmacodynamic Study on siRNA Liposome for Injection in Gene Transferred Mice Model

目的利用乙型肝炎病毒(HBV)转基因鼠模型,研究注射用小干扰核糖核酸(siRNA)脂质体药物的抗HBV作用。方法对M-TgHBV转基因小鼠静脉给予不同剂量的注射用siRNA脂质体药物,在给药的不同时间点采血测定乙型肝炎病毒表面抗原(HBsAg),在最后一天取部分鼠肝脏进行免疫组化分析。结果与给药前比较,试验药物2mg/kg组(A组)HBsAg表达水平在第9天和第12天时明显降低(P<0.05),在第15天时降低非常明显(P<0.01),试验药物1mg/kg及0.5mg/kg组(B,C组)、阳性药物(拉米夫定)组(F组)在第15天时均显著降低(P<0.05);免疫组化分析结果表明,相对于阴性对照组(G组),肝内HBsAg表达抑制率A组为48.44%,B组为36.73%。结论注射用siRNA脂质体在转基因鼠中的抗HBV作用明显。

Objective To research the inhibitory effects of injectable liposome siRNA （small interference RNA） drug on hepatitis B virus （HBV） by HBV transgenic mice mode. Methods M-TgHBV transgenic mice were intravenously injected with different doses of liposome siRNA injection, the HBsAg values were measured at different intervals and the livers of certain mice were proceeded with immunohistochemical analysis on the last day. Results The HBsAg expression level of group A on the 9th day and 12th day markedly reduced in comparison with that before drug treatment （P 〈0.05）, and unusually reduced on the 15th day （P 〈0.01）. The HBsAg expression level of group F,group B and group C was obviously lower than that before drug treatment （P〈0.05）.The irnmunohistochemical analysis results indicated that group A and group B possessed the inhibitory rate of 48.44% and 36.73% to HBsAg expression respectively. Conclusion Liposome siRNA injection has a significant inhibition on HBV transgenic mice mode.